{"id":104327,"date":"2018-03-11T10:27:18","date_gmt":"2018-03-11T10:27:18","guid":{"rendered":"https:\/\/www.deberes.net\/tesis\/sin-categoria\/mecanismos-moleculares-y-fisiopatologicos-de-la-mitofagia-en-el-sa%c2%adndrome-melas\/"},"modified":"2018-03-11T10:27:18","modified_gmt":"2018-03-11T10:27:18","slug":"mecanismos-moleculares-y-fisiopatologicos-de-la-mitofagia-en-el-sa%c2%adndrome-melas","status":"publish","type":"post","link":"https:\/\/www.deberes.net\/tesis\/biologia-humana\/mecanismos-moleculares-y-fisiopatologicos-de-la-mitofagia-en-el-sa%c2%adndrome-melas\/","title":{"rendered":"Mecanismos moleculares y fisiopatol\u00f3gicos de la mitofagia en el s\u00edndrome melas"},"content":{"rendered":"<h2>Tesis doctoral de <strong> David Cot\u00e1n Mar\u00edn <\/strong><\/h2>\n<p>Una importante cantidad de enfermedades humanas consideradas raras son causadas por mutaciones en el dna mitocondrial. Una de estas enfermedades raras es el s\u00edndrome melas (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) com\u00fanmente causado por mutaciones puntuales en genes que codifican para trna en el dna mitocondrial. En este trabajo se estudia como esta mutaci\u00f3n afecta a la funci\u00f3n mitocondrial en cultivos de fibroblastos primarios pertenecientes a dos pacientes con el s\u00edndrome melas que contienen un cambio de base a3243g en el gen trna leu (uur). En ambos cultivos primarios, la actividad enzim\u00e1tica mitocondrial y los niveles de coenzima q (coq) se encuentran disminuidos significativamente. Una disminuci\u00f3n similar encontramos en el potencial de membrana mitocondrial de estos fibroblastos melas. La disfunci\u00f3n mitocondrial est\u00e1 asociada a un incremento del estr\u00e9s oxidativo y la apertura del poro mitocondrial y aumento de su permeabilidad, que desencadena en una degradaci\u00f3n selectiva de mitocondrias malfuncionantes por mitofagia. Estudios de microscop\u00eda electr\u00f3nica confirman una masiva degradaci\u00f3n de mitocondrias alteradas por este mecanismo de autofagia selectiva. C\u00edbridos transmitocondriales que albergan la misma mutaci\u00f3n a3243g tambi\u00e9n muestran una deficiencia de coq y un incremento en la actividad mitof\u00e1gica.   todas estas anormalidades fueron parcialmente restauradas con una suplementaci\u00f3n de coq. La autofagia en fibroblastos melas fue tambi\u00e9n eliminada tras el tratamiento con antioxidantes o ciclosporina, sugiriendo que tanto las especies reactivas de ox\u00edgeno (ros) como la permeabilidad del poro mitocondrial (mpt), participan en este proceso. Adem\u00e1s, la prevenci\u00f3n de la autofagia en fibroblastos de pacientes melas con 3-methyl adenine o wortmanina, as\u00ed como el silenciamiento del gen atg5, un esencial gen autof\u00e1gico, por peque\u00f1os rnas de interferencia (sirnas) result\u00f3 en un aumento en la muerte celular, lo que sugiere un papel protector de la autofagia en fibroblastos melas.<\/p>\n<p>&nbsp;<\/p>\n<h3>Datos acad\u00e9micos de la tesis doctoral \u00ab<strong>Mecanismos moleculares y fisiopatol\u00f3gicos de la mitofagia en el s\u00edndrome melas<\/strong>\u00ab<\/h3>\n<ul>\n<li><strong>T\u00edtulo de la tesis:<\/strong>\u00a0 Mecanismos moleculares y fisiopatol\u00f3gicos de la mitofagia en el s\u00edndrome melas <\/li>\n<li><strong>Autor:<\/strong>\u00a0 David Cot\u00e1n Mar\u00edn <\/li>\n<li><strong>Universidad:<\/strong>\u00a0 Pablo de olavide<\/li>\n<li><strong>Fecha de lectura de la tesis:<\/strong>\u00a0 19\/10\/2010<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<h3>Direcci\u00f3n y tribunal<\/h3>\n<ul>\n<li><strong>Director de la tesis<\/strong>\n<ul>\n<li>Jos\u00e9 Antonio S\u00e1nchez Alc\u00e1zar<\/li>\n<\/ul>\n<\/li>\n<li><strong>Tribunal<\/strong>\n<ul>\n<li>Presidente del tribunal: pl\u00e1cido Navas lloret <\/li>\n<li>Mar\u00eda Mor\u00e1n bermejo (vocal)<\/li>\n<li>Juan  Jos\u00e9 Infante vi\u00f1olo (vocal)<\/li>\n<li>nadezda Apostolova atanasovska (vocal)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Tesis doctoral de David Cot\u00e1n Mar\u00edn Una importante cantidad de enfermedades humanas consideradas raras son causadas por mutaciones en el 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